Comparisons were made of the protective activity of ICRF-187 and a series of related bis-dioxopiperazine analogues against the acute toxicity produced by daunomycin (daunorubicin) in Syrian golden hamsters. The protective activity was found not to be stereospecific with respect to the 1- and the d-isomer of ICRF-159, namely, ICRF-186 and ICRF-187. Protection was minimal or absent when the hamsters were pretreated with various doses of ICRF analogues in which slight changes had been made in the dioxopiperazine rings or in the central chain. Thus, very little alteration can occur in the basic structure of ICRF-187 without loss of its protective activity against anthracycline cardiotoxicity.